NM_004797.4:c.-8-3963G>A

Variant names:

• chr3-186849088-G-A
• rs822396
• NM_004797.4:c.-8-3963G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004797.4(ADIPOQ):​c.-8-3963G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,116 control chromosomes in the GnomAD database, including 50,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50365 hom., cov: 31)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• Publications: 106 publications found

Genes affected

ADIPOQ (HGNC:13633): (adiponectin, C1Q and collagen domain containing) This gene is expressed in adipose tissue exclusively. It encodes a protein with similarity to collagens X and VIII and complement factor C1q. The encoded protein circulates in the plasma and is involved with metabolic and hormonal processes. Mutations in this gene are associated with adiponectin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Apr 2010]

ADIPOQ Gene-Disease associations (from GenCC):

• STAT3-related early-onset multisystem autoimmune disease

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	NM_004797.4	MANE Select	c.-8-3963G>A		intron	N/A	NP_004788.1	Q15848
	ADIPOQ	NM_001177800.2		c.-9+3481G>A		intron	N/A	NP_001171271.1	A8K660

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	ENST00000320741.7	TSL:1 MANE Select	c.-8-3963G>A		intron	N/A	ENSP00000320709.2	Q15848
	ADIPOQ	ENST00000444204.2	TSL:1	c.-9+3481G>A		intron	N/A	ENSP00000389814.2	Q15848
	ADIPOQ	ENST00000881747.1		c.-9+3481G>A		intron	N/A	ENSP00000551806.1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123632 AN: 151998 Hom.: 50310 Cov.: 31

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.831

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.813 AC: 123746 AN: 152116 Hom.: 50365 Cov.: 31 AF XY: 0.814 AC XY: 60545 AN XY: 74364

African (AFR) AF: 0.797 AC: 33085 AN: 41490

American (AMR) AF: 0.840 AC: 12839 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2972 AN: 3472

East Asian (EAS) AF: 0.891 AC: 4608 AN: 5172

South Asian (SAS) AF: 0.795 AC: 3835 AN: 4824

European-Finnish (FIN) AF: 0.819 AC: 8655 AN: 10566

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55038 AN: 67982

Other (OTH) AF: 0.833 AC: 1760 AN: 2114

Alfa AF: 0.816 Hom.: 216492

Bravo AF: 0.817

Asia WGS AF: 0.878 AC: 3053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.23
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs822396; hg19: chr3-186566877;